Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000473361 | SCV000546134 | uncertain significance | Hereditary hemorrhagic telangiectasia | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 108 of the ENG protein (p.His108Tyr). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 25312062). ClinVar contains an entry for this variant (Variation ID: 407139). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change does not substantially affect ENG function (PMID: 25312062). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Laboratory for Molecular Medicine, |
RCV000600129 | SCV000713059 | uncertain significance | not specified | 2017-04-03 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.His108Tyr (c. 321_322delinsTT) variant in ENG results from a deletion and insertion of 2 conse cutive bases in cis and creates a missense change. This variant has been reporte d in 1 French individual with Hereditary Hemorrhagic Telangiectasia (HHT); howev er, this individual carried a second variant in ENG that was sufficient to expla in their disease (Mallet 2015). The p.His108Tyr variant has also been identified in 15/66242 European chromosomes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs756897517). In vitro functional studies pro vide some evidence that this change may not impact protein function (Mallet 2015 ). However, these types of assays may not accurately represent biological functi on. In summary, while the clinical significance of the p.His108Tyr variant is un certain, these data suggest that it is more likely to be benign. |
| Ambry Genetics | RCV002323702 | SCV002610349 | likely benign | Cardiovascular phenotype | 2017-02-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV002489031 | SCV002783672 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 1 | 2022-01-28 | criteria provided, single submitter | clinical testing |